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Seizures. Esmailian Mehrdad MD Faculty Member of Esfahan University. Terminology. Seizures: an episode of neurologic dysfunction caused by abnormal neuronal activity that results in a sudden change in behavior, sensory perception, or motor activity

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    1. Seizures Esmailian Mehrdad MD Faculty Member of Esfahan University

    2. Terminology • Seizures: an episode of neurologic dysfunction caused by abnormal neuronal activity that results in a sudden change in behavior, sensory perception, or motor activity • Convulsions: Seizures with prominent body movement • Non-convulsive seizures: Seizures with minimal or no body movement • Epilepsy: recurrent, unprovoked seizures from known or unknown causes • Epilepsy syndromes:Groups of epileptic patterns of varying cause but similar course and response to treatment

    3. Ictus : describes the period in which the seizure occurs • post-ictal : refers to the period after the seizure has ended but before the patient has returned to his or her baseline mental status • Focal or partialseizure : describes abnormal neuronal firing that is limited to one hemisphere or area of the brain that manifests itself as seizure activity on one side of the body or one extremity • simple partial : no change in mental status • complex partial : with some degree of impaired consciousness

    4. Generalized seizure :abnormal electrical activity involving both cerebral hemispheres that causes an alteration in mental status • status epilepticus (SE) : 30 minutes of continuous seizure activity or a series of seizures without a return to full consciousness or duration of 5 continuous minutes of generalized seizure activity or 2 or more separate seizure episodes without return to baseline

    5. Pathophysiology • Abnormal neuronal firing due to biochemical imbalance between excitatory neurotransmitters and the NMDA receptor and inhibitory forces (GABA) at the neuronal cell membran repeated, abnormal electrical discharges that may stay within a certain area of the brain or they may propagate throughout the brain resulting in generalized seizures

    6. Complications • Seizures produce a number of physiologic changes due to catecholamine surge • During a generalized seizure, there can be a period of transient apnea and subsequent hypoxia • In a physiological effort to maintain appropriate cerebral oxygenation, the patient may become hypertensive • Transient hyperthermia may occur in up to 40% of patients and is thought to result from vigorous muscle activity that occurs in a seizure • Hyperglycemia and lactic acidosisoccur within minutes of a convulsive episode and usually resolve within 1 hour

    7. Transient leukocytosis may also be seen but is not accompanied by bandemia (unless infection is present) • In the setting of status epilepticus, there is pronounced systemic decompensation including hypoxemia, hypercarbia, hypertension followed by hypotension, hyperthermia, depletion of cerebral glucose and oxygen, cardiac dysrhythmias, and rhabdomyolysis. These changes may even take place despite adequate oxygenation and ventilation. In extremis, pulmonary edema and disseminated intravascular coagulation (DIC) have also been reported

    8. Frequency • Epilepsy and seizures affect more than 3 million American of all ages • Approximately 200,000 new cases occur each year, of which 40-50% will recur be classified as epilepsy • Overall, approximately 50,000-150,000 cases will reach status epilepticu • Males are slightly more likely to develop epilepsy than female • Incidence is highest in those younger than 2 years and in those older than 65 years

    9. Mortality/Morbidity • Up to 50% of patients with epilepsy will have recurrent seizures despite medical therapy • Up to 25% of patients with a first-time, generalized seizure will have a recurrence within 2 years • The overall mortality rate is about 20% for those who reach status epilepticus • The mortality rates are highest for those older than 75 years, reflecting an increased incidence of degenerative, neoplastic, and vascular pathologies

    10. History • Recent noncompliance with medications • History of CNS pathology (stroke, neoplasms, recent surgery) • History of systemic neoplasms, infections, metabolic disorders, or toxic ingestions • Recent trauma or fall • Alcohol abuse • Recent travel or immigration to the United States • Pregnancy • Focal symptoms (partial seizure activity) that then progressed to a generalized seizure

    11. P/E • General Condition : • A generalized seizure is recognizable at the bedside when tonic-clonic activity is present • If the patient is actively seizing, attempt to observe motor activity, as posturing (decerebrate/decorticate) and eye deviation may provide clues to the epileptic focus • A partial seizure may present as isolated seizure activity with or without loss of consciousness. The workup for partial seizures is more extensive and requires neurologic consultation • Identifying a partial seizure that then generalizes to a full tonic-clonic seizure may be difficult, as this may be missed as the initial presentation of a generalized seizure

    12. Vital signs : • In a generalized, tonic-clonic seizure, accurate vital signs are difficult to obtain • Low-grade fever may be present initially, but prolonged fever may be an indication of infectious etiology • Mental status examination : • As mentioned above, any seizure with loss of consciousness is termed complex

    13. Neurologic examination : • Focal deficits may be evidence of an old lesion, new pathology, or Todd’s paralysis (transient, <24 h paralysis that mimics stroke) • Hyperreflexia and extensor plantar responses are indicative of a recent seizure but should resolve during the post-ictal period

    14. Causes • known seizure disorder : • subtherapeutic levels of antiepileptic medications, including the following:  • Medical noncompliance • Systemic derangement that may disrupt absorption, distribution, and metabolism of medication (infection) • Stress, lack of sleep, and caffeine use

    15. New-onset seizure disorder : • CNS pathologies (stroke, neoplasm, trauma, hypoxia, vascular abnormality) • Metabolic abnormalities (hypoglycemia/hyperglycemia, hyponatremia/hypernatremia, hypercalcemia, hepatic encephalopathy) • Toxicologic etiologies (alcohol withdrawal , cocaine , isoniazid , theophylline) • Infection etiologies (meningitis, encephalitis, brain abscess , neurocysticercosis and malaria)

    16. Differential Diagnoses • Delirium Tremens • Delirium, Dementia, and Amnesia • Eclampsia • Encephalitis • Epidural and Subdural Infections • Febrile Seizures • Fugue States • Heat Exhaustion • Heatstroke • Hyperventilation Syndrome • Hypoglycemia

    17. Hyponatremia • Hypothyroidism and Myxedema Coma • Malingering • Meningitis • Migraine Narcolepsy/Cataplexy • Movement Disorders in Individuals with Developmental Disabilities • Night terrors • Paroxysmal Vertigo • Stroke, Hemorrhagic • Stroke, Ischemic • Subarachnoid Hemorrhage

    18. Syncope • Toxicity, Anticholinergic • Toxicity, Antidepressant • Toxicity, Antihistamine • Toxicity, Carbon Monoxide • Toxicity, Cyclic Antidepressants • Toxicity, Isoniazid • Transient Global Amnesia • Transient Ischemic Attack • Trauma • Withdrawal Syndromes

    19. Seizure Types • Partial (focal, local) seizures   Simple partial seizures (consciousness maintained)    With motor signs   With autonomic symptoms and signs   With somatosensory or special sensory symptoms • Complex partial seizures (consciousness impaired)    Partial seizures evolving to secondary generalized tonic- clonic seizures

    20. Generalized seizures (convulsive and nonconvulsive • Absence seizures (consciousness impaired, clonic, tonic, tonic or autonomic component) • Atypical absence (marked change in tone, not rapid in onset or cessation) • Myoclonic seizures • Clonic seizures • Tonic seizures • Tonic-clonic seizures • Atonic seizures • Unclassified epileptic seizures (includes all seizures that cannot be classified because of inadequate or incomplete data)

    21. Classification of Epileptic Syndromes I.    Idiopathic epileptic syndromes (focal or generalized) A.    Benign neonatal convulsionsB.    Benign childhood epilepsy 1.    Central midtemporal spikes (benign rolandic epilepsy of childhood) 2.    Occipital spikesC.    Childhood/juvenile absence epilepsyD.    Juvenile myoclonic epilepsyE.    Idiopathic epilepsy—otherwise unspecified

    22. II.  Symptomatic epilepsy syndromes (focal or generalized) A.    West syndrome (infantile spasms)B.    Lennox-Gastaut syndromeC.    Early myoclonic encephalopathyD.    Epilepsia partialis continuaE.    Acquired epileptic aphasia (Landau-Kleffner syndrome)F.    Temporal lobe epilepsyG.    Frontal lobe epilepsyH.    Posttraumatic epilepsyI.    Other symptomatic epilepsy, not otherwise specified

    23. III.  Other epilepsy syndromes of uncertain or mixed classification A.    Neonatal seizuresB.    Febrile seizuresC.    Reflex epilepsyD.    Other unspecified

    24. Laboratory Studies • Clinical information should guide the specific workup of a patient • Studies have shown a low yield for extensive laboratory tests in the evaluation of a patient presenting with a first-time, single seizure • An ACEP Clinical Policy recommends the following in adults with new-onset seizure: • Serum glucose level • Serum sodium level • Pregnancy test in women of childbearing age

    25. For patients with a first-time, generalized tonic-clonic seizure, obtain a chem 7 (electrolyte panel) and urine or serum pregnancy test • For patients with known seizure disorder who are currently taking medications, blood levels of antiepileptic medications should be obtained • For patients with a history of malignancy, serum calcium levels should be obtained

    26. Toxicologic testing  • No evidence suggests that such testing changes outcomes • Toxicologic testing may be beneficial for help with future medical and psychiatric management • An arterial blood gas (ABG) measurement has limited clinical utility for the patient in status epilepticus because it will likely reveal metabolic acidosis but should rapidly correct after the patient stops seizing

    27. Imaging Studies • Computed tomography • For patients with new-onset seizures or those in statusepilepticus, noncontrast head CT in the ED is the imaging procedure of choice because of availability and ability to identify potential catastrophic pathologies • For the patient who presents for first-time, generalized tonic-clonic seizure that has returned to baseline mental status with a normal neurologic examination and who has no comorbidities, CT may be completed as on outpatient basis provided follow-up is ensured. However, because of the availability and speed of CT scanning in the ED, routine CT scanning for first-time seizure is strongly recommended.

    28. For any partial seizure or suspected intracranial process (trauma, history of malignancy, immunocompromise, or anticoagulation, new focal neurologic examination, age >40 y), then a head CT should be performed emergently • Approximately 3-41% of patients with first-time seizures will have abnormal head CT findings • In patients with a known seizure disorder, consider a head CT if any of the following are present: new focal deficits, trauma, persistent fever, new character or pattern to the seizures, suspicion for AIDS, infection, or anticoagulation

    29. MRI • A better diagnostic test because of higher yield and ability to identify smaller lesions, but availability from the ED may be a limiting factor. In addition, MRI is time-consuming and may interfere with adequate patient monitoring

    30. Electrocardiography (ECG) : • Seizure activity can be precipitated by cerebral hypoperfusion from an arrhythmia. The ECG may identify the following: • Prolonged QTc • Widened QRS • Prominent R in aVR • Heart block

    31. Electroencephalography • Electroencephalography (EEG) is not routinely available in the ED. • EEG should be part of the full neurodiagnostic workup, as it has substantial yield and ability to predict risk of seizure recurrence • In the ED, EEG should be considered if available and if the patient is paralyzed, is intubated, or is in refractory status epilepticus to ensure that seizure activity is controlled.

    32. Lumbar puncture:  • Immunocompromised patients • persistent fever • severe headache • persistently altered mental status

    33. Treatment • Prehospital Care : • Care is mostly supportive, as most seizures are short duration, especially pediatric simple febrile seizures (keep the person away from dangerous situations/speak quietly and reassuringly; use restraint only if necessary for safety) • ABCs, including oxygenation and airway assessment, temperature assessment, blood glucose assessment, and spinal precautions, should be performed as needed • Intravenous access should be obtained for almost all patients (may be deferred in those with simple febrile seizures) • EMS protocols should include benzodiazepines (either IV, IM, or rectal) for prolonged seizures or status epilepticus

    34. Emergency Department Care : • Care should be individualized for the patient presenting with seizure • Sometimes, the most difficult part of the ED evaluation is differentiating whether the patient has had a seizure. Clues to the diagnosis include a clear history of tonic-clonic movements, urinary or bowel incontinence, post-episode confusion, and tongue biting • Attempt to obtain history from EMS providers, family, friends, or observers who may have been present during the episode • For those who present with a witnessed seizure who have stopped seizing, supportive care is adequate 

    35. If antiepileptic medication levels are found to be low, then a loading dose given in the ED and discharge home is appropriate as long as there are no other concerning features to the presentation • Phenytoin is an extremely common antiepileptic medication and is classically given as "one gram" in the ED, sometimes with the medication being delivered as half oral and half parenteral. Oral absorption of the drug can be erratic, but, when given in the appropriate doses (15-20 mg/kg PO either as a single dose or divided into 400-600 mg per dose every 2 h), it can achieve therapeutic serum levels

    36. Both valproic acid and phenobarbital can also be given parenterally as a loading dose at 20 mg/kg • Carbamazepine has proven to be effective for oral loading, but it is associated with a high rate of adverse effects. Therefore, oral loading is not recommended at this time • Newer antiepileptic drugs, such as lamotrigine and levetiracetam, have varying drug profiles and are still being studied. Doses of these medications should be given in consultation with a neurologist

    37. Patient's seizure activity : • ABCs should be addressed, as detailed below: • Airway management • Administer oxygen. • For patients who are in status epilepticus or cyanotic, endotracheal intubation using rapid sequence intubation (RSI) should be strongly considered • If using RSI, short-acting paralytics should be used to ensure that ongoing seizure activity is not masked • Consider EEG monitoring in the ED if the patient has been paralyzed because there is no other method to determine if seizure activity is still present

    38. Establish large-bore intravenous access • Initiate rapid glucose determination and treat appropriately • Consider antibiotics with or without antiviral agents, depending on the clinical situation • The goal of treatment is to control the seizure before neuronal injury occurs (theoretically between 20 min to 1 h) • CNS infections and anoxic injury are the leading causes of mortality associated with status epilepticus

    39. Medication • Earlier treatment is more effective than later treatment in halting status epilepticus • Benzodiazepine, notably lorazepam (Ativan), is the initial class of drug for the treatment of status epilepticus.  • Phenytoin or fosphenytoin (Cerebyx) is the next drug to be administered when a second drug is needed • Failure to respond to optimal benzodiazepine and phenytoin loading operationally defines refractory status epilepticus

    40. No data clearly support a best third-line drug, controlled trials are lacking, and recommendations vary greatly. The list of third-line drugs includes barbiturates, propofol, valproate, levetiracetam, and lidocaine • A general principle is to maximize benzodiazepine and phenytoin dosages before adding an additional agent • Many of these drugs are classified as category D in pregnancy. However, these drugs may be used in life-threatening situations, such as generalized convulsive status epilepticus (GCSE)

    41. Benzodiazepines • Considered first-line therapy • Intravenous options include lorazepam, diazepam, and midazolam • If intravenous access cannot be obtained, then IMlorazepam or midazolam, or rectal diazepam can be considered • Intravenous lorazepam was found to be superior to intravenous diazepam in both seizure cessation and preventing recurrent seizures • A common regimen is 0.1 mg/kg of lorazepam (Ativan) IV given at 2 mg/min or 0.2 mg/kg diazepam IV given at 5-10 mg/min

    42. Very large doses of benzodiazepines may be needed • There is no specific upper limit to benzodiazepine dose when used for acute seizure control • As with all sedatives, monitor the patient for respiratory or cardiovascular depression

    43. Phenytoin • Usually considered the second-line agent for patients who continue to seize despite aggressive benzodiazepine therapy • The recommended dose is 20 mg/kg IV and can be augmented with another 10 mg/kg IV if the patient is still seizing • Care should be taken with the administration of parenteral phenytoin because the propylene glycol diluent may cause hypotension, cardiac arrhythmias, and death if given too quickly

    44. Fosphenytoin • Fosphenytoin is a phenytoin precursor that is considered to be safer than phenytoin by some authors as it does not contain a propylene glycol diluent. • Other authors have disputed a safety advantage for fosphenytoin, and it is much more expensive than phenytoin • Fosphenytoin may be administered intramuscularly, and this is an advantage for patients without intravenous access

    45. Valproic acid • Effective in treating all forms of seizure • Recommended dose of valproic acid is 15-20 mg/kg • Valproic acid has an excellent safety profile • It is contraindicated in hepatic dysfunction because of the extremely rare occurrence of fatal idiosyncratic hepatotoxicity

    46. Phenobarbital • Similar efficacy to lorazepam • Recommended dose of phenobarbital is 20 mg/kg, but, like phenytoin, it can be given up to 30 mg/kg for severe refractory seizures • Phenobarbital may cause hypotension and respiratory depression

    47. Continuous infusions • If 2 or more of the initial drug therapies fail to control the seizures, then the next line of treatment includes continuous infusions of antiepileptic medications. The major side effects are hypotension and respiratory depression, and the patient should be intubated (if not already completed up to this point) and preparation made to support the patient's cardiovascular status • There is very little evidence to guide use of these medications. • Midazolam is slightly less effective at stopping seizures versus propofol or pentobarbital, but treatment with midazolam has a lower frequency of occurrence of hypotension

    48. Pentobarbital • Pentobarbital is shorter acting than phenobarbital, but it is more sedating • Pentobarbital should be administered in a bolus at 5-15 mg/kg, then continuous infusion of 0.5-10 mg/kg/h as tolerated • Midazolam: • administered as a 0.2 mg/kg bolus, then continuous infusion of 0.05-2 mg/kg/h